6pt3 | pdb_00006pt3

Crystal structure of the active delta opioid receptor in complex with the small molecule agonist DPI-287

spinqualitylabelsall models 6pt3, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pt3 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: OWY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Selective activation of the delta-opioid receptor (DOP) has great potential for the treatment of chronic pain, benefitting from ancillary anxiolytic and antidepressant-like effects. Moreover, DOP agonists show reduced adverse effects as compared to mu-opioid receptor (MOP) agonists that are in the spotlight of the current "opioid crisis." Here, we report the first crystal structures of the DOP in an activated state, in complex with two relevant and structurally diverse agonists: the potent opioid agonist peptide KGCHM07 and the small-molecule agonist DPI-287 at 2.8 and 3.3 A resolution, respectively. Our study identifies key determinants for agonist recognition, receptor activation, and DOP selectivity, revealing crucial differences between both agonist scaffolds. Our findings provide the first investigation into atomic-scale agonist binding at the DOP, supported by site-directed mutagenesis and pharmacological characterization. These structures will underpin the future structure-based development of DOP agonists for an improved pain treatment with fewer adverse effects. Elucidating the active delta-opioid receptor crystal structure with peptide and small-molecule agonists.,Claff T, Yu J, Blais V, Patel N, Martin C, Wu L, Han GW, Holleran BJ, Van der Poorten O, White KL, Hanson MA, Sarret P, Gendron L, Cherezov V, Katritch V, Ballet S, Liu ZJ, Muller CE, Stevens RC Sci Adv. 2019 Nov 27;5(11):eaax9115. doi: 10.1126/sciadv.aax9115. eCollection, 2019 Nov. PMID:31807708 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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